During the aging process, physical capabilities (e.g., muscular strength) and cognitive functions (e.g., memory) gradually decrease. Regarding cognitive functions, substantial functional (e.g., ...compensatory brain activity) and structural changes (e.g., shrinking of the hippocampus) in the brain cause this decline. Notably, growing evidence points towards a relationship between cognition and measures of muscular strength and muscle mass. Based on this emerging evidence, resistance exercises and/or resistance training, which contributes to the preservation and augmentation of muscular strength and muscle mass, may trigger beneficial neurobiological processes and could be crucial for healthy aging that includes preservation of the brain and cognition. Compared with the multitude of studies that have investigated the influence of endurance exercises and/or endurance training on cognitive performance and brain structure, considerably less work has focused on the effects of resistance exercises and/or resistance training. While the available evidence regarding resistance exercise-induced changes in cognitive functions is pooled, the underlying neurobiological processes, such as functional and structural brain changes, have yet to be summarized. Hence, the purpose of this systematic review is to provide an overview of resistance exercise-induced functional and/or structural brain changes that are related to cognitive functions.
A systematic literature search was conducted by two independent researchers across six electronic databases; 5957 records were returned, of which 18 were considered relevant and were analyzed.
Based on our analyses, resistance exercises and resistance training evoked substantial functional brain changes, especially in the frontal lobe, which were accompanied by improvements in executive functions. Furthermore, resistance training led to lower white matter atrophy and smaller white matter lesion volumes. However, based on the relatively small number of studies available, the findings should be interpreted cautiously. Hence, future studies are required to investigate the underlying neurobiological mechanisms and to verify whether the positive findings can be confirmed and transferred to other needy cohorts, such as older adults with dementia, sarcopenia and/or dynapenia.
The study of human motion dates back more than 2000 years. With the event of information technology, new areas have been added to this field. Research using computer vision and computer graphics ...contributes to a transformation of biomechanics into a discipline that now applies computing technology throughout, on the other hand, computer vision and computer graphics also benefit from defining goals aimed at solving problems in biomechanics. Besides interactions, all three areas also developed their own inherent research dynamics towards studying human motion. Researchers from all three of these areas have contributed to this book to promote the establishment of human motion research as a multi-facetted discipline and to improve the exchange of ideas and concepts between these three areas. Some chapters review the state of the art whilst others report on leading edge research results, with applications in medicine, sport science, cinematography and robotics.
Recently two approaches were reported that addressed a vitally important problem in regenerative medicine, i. e. the successful treatment of wounds even under diabetic conditions. Accordingly, these ...studies with diabetic rabbits Sarojini et al. PLoS One 2017, 12(4):e0174899 and diabetic mice Müller et al. Polymers 2017, 9, 300 identified a novel (potential) target for the acceleration of wound healing in diabetes. Both studies propose a raise of the intracellular metabolic energy status via exogenous administration either of ATP, encapsulated into lipid vesicles, or of polyphosphate (polyP) micro-/nanoparticles. Recently this physiological polymer, polyP, was found to release metabolic energy in form of ATP into both the extra- and also intra-cellular space. In the present work the uptake mechanism of the amorphous polyP microparticles "Ca-polyP-MP" has been described and found to be a clathrin-dependent endocytosis import, based on inhibition studies with the inhibitor trifluoperazine, which blocks the clathrin-dependent endocytosis import. The experiments had been performed with SaOS-2 cells, by studying the uptake and distribution of the electron-dense particles into the cells, and with HUVEC cells, for analysis of the intracellular accumulation of polyP, visualized by fluorescent staining of polyP. Concurrently with the uptake of particular polyP the intracellular ATP level increased as well. In contrast to "Ca-polyP-MP" the soluble polyP, administered as "Na-polyPCa2+", did not cause an increase in the intracellular Ca2+ level, suggesting a different mode of action of these two forms of polyP. Based on existing data on the effect of polyP and ATP on the induction of vascularization during wound repair, both groups (Sarojini et al. and Müller et al.) propose that the acceleration of wound repair is based on an increased metabolic energy supply directly to the regenerating wound area.
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Here we describe the formulation of a morphogenetically active bio-ink consisting of amorphous microparticles (MP) prepared from Ca2+ and the physiological inorganic polymer, ...polyphosphate (polyP). Those MP had been fortified by mixing with poly-ε-caprolactone (PCL) to allow 3D-bioprinting. The resulting granular PCL/Ca-polyP-MP hybrid material, liquefied by short-time heating to 100 °C, was used for the 3D-printing of tissue-like scaffolds formed by strands with a thickness of 400 µm and a stacked architecture leaving ≈0.5 mm2-sized open holes enabling cell migration. The printed composite scaffold turned out to combine suitable biomechanical properties (Young’s modulus of 1.60 ± 0.1 GPa; Martens hardness of 153 ± 28 MPa), matching those of cortical and trabecular bone, with morphogenetic activity. This scaffold was capable of attracting and promoting the growth of human bone-related SaOS-2 cells as demonstrated by staining for cell viability (Calcein AM), cell density (DRAQ5) and SEM studies. Furthermore, the hybrid material was demonstrated to upregulate the steady-state-expression of the cell migration-inducing chemokine SDF-1α. EDX analysis and FTIR measurements revealed the presence of hydroxyapatite in the mineral deposits formed on the scaffold surface. Based on the results we conclude that granular PCL/Ca-polyP-MP hybrid material is suitable for the fabrication of bioprintable scaffold which comprises not only biomechanical stability but also morphogenetic potential.
In present-day regenerative engineering efforts, biomaterial- and cell-based strategies are proposed that meet the required functional and spatial characteristics and variations, especially in the transition regions between soft (cartilage, tendon or ligament) and hard (bone) tissues.
In a biomimetic approach we succeeded to fabricate amorphous Ca-polyP nanoparticles/microparticles which are highly biocompatible. Together with polycaprolactone (PCL), polyP can be bio-printed. This hybrid material attracts the cells, as documented optically as well as by a gene-expression studies. Since PCL is already a FDA-approved organic and inert polymer and polyP a physiological biologically active component this new bio-hybrid material has the potential to restore physiological functions, including bone remodelling and regeneration if used as implant.
We analyze the two-dimensional distribution and kinematics of the stars as well as molecular and ionized gas in the central few hundred parsecs of five active and five matched inactive galaxies. The ...equivalent widths of the Brgamma line indicate that there is no ongoing star formation in their nuclei, although recent (terminated) starbursts are possible in the active galaxies. The stellar velocity fields show no signs of non-circular motions, while the 1-0 S(1) H sub(2) kinematics exhibit significant deviations from simple circular rotation. In the active galaxies the H sub(2) kinematics reveal inflow and outflow superimposed on disk rotation. Steady-state circumnuclear inflow is seen in three active galactic nuclei (AGNs), and hydrodynamical models indicate it can be driven by a large-scale bar. In three of the five AGNs, molecular outflows are spatially resolved. The outflows are oriented such that they intersect, or have an edge close to, the disk, which may be the source of molecular gas in the outflow. The relatively low speeds imply the gas will fall back onto the disk, and with moderate outflow rates, they will have only a local impact on the host galaxy. H sub(2) was detected in two inactive galaxies. These exhibit chaotic circumnuclear dust morphologies and have molecular structures that are counter-rotating with respect to the main gas component, which could lead to gas inflow in the near future. In our sample, all four galaxies with chaotic dust morphology in the circumnuclear region exist in moderately dense groups with 10-15 members where accretion of stripped gas can easily occur.
The proliferation marker Ki67 has been suggested as a promising cancer biomarker. As Ki67 needs an exact quantification, this marker is a prototype of a new generation of tissue-based biomarkers. In ...this study, we have systematically evaluated different cut points for Ki67 using three different clinical end points in a large neoadjuvant study cohort.
We have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast cancer core biopsies from the neoadjuvant GeparTrio trial. We used the standardized cutoff-finder algorithm for three end points response to neoadjuvant chemotherapy (pCR), disease-free (DFS) and overall-survival (OS). The analyses were stratified for hormone receptor (HR) and HER2 status by molecular subtype radar diagrams (MSRDs).
A wide range of Ki67 cut points between 3%–94% (for pCR), 6%–46% (for DFS) and 4%–58% (for OS) were significant. The three groups of Ki67 ≤ 15% versus 15.1%–35% versus >35% had pCR-rates of 4.2%, 12.8%, and 29.0% (P < 0.0005), this effect was also present in six of eight molecular subtypes. In MSRD, Ki67 was significantly linked to prognosis in uni- and multivariate analysis in the complete cohort and in HR-positive, but not triple-negative tumors.
Ki67 is a significant predictive and prognostic marker over a wide range of cut points suggesting that data-derived cut point optimization might not be possible. Ki67 could be used as a continuous marker; in addition, the scientific community could define standardized cut points for Ki67. Our analysis explains the variability observed for Ki67 cut points in previous studies; however, this should not be seen as weakness, but as strength of this marker. MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer. The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers.
The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and other biomarkers, has been demonstrated to be a marker of response to ...immune-checkpoint therapy in several cancers. Pathologists have therefore started to devise standardized visual approaches to quantify TILs for therapy prediction. However, despite successful standardization efforts visual TIL estimation is slow, with limited precision and lacks the ability to evaluate more complex properties such as TIL distribution patterns. Therefore, computational image analysis approaches are needed to provide standardized and efficient TIL quantification. Here, we discuss different automated TIL scoring approaches ranging from classical image segmentation, where cell boundaries are identified and the resulting objects classified according to shape properties, to machine learning-based approaches that directly classify cells without segmentation but rely on large amounts of training data. In contrast to conventional machine learning (ML) approaches that are often criticized for their "black-box" characteristics, we also discuss explainable machine learning. Such approaches render ML results interpretable and explain the computational decision-making process through high-resolution heatmaps that highlight TILs and cancer cells and therefore allow for quantification and plausibility checks in biomedical research and diagnostics.
An examination of marine organisms with disulfide- and multisulfide-containing metabolites is presented. Polysulfides from various marine organisms exhibit different biological activities.
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